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Immunostimulating RNA Delivered by P1500 PEGylated Cationic Liposomes Limits Influenza Infection in C57Bl/6 Mice

The emergence of highly pathogenic viruses and a high speed of infection spread put forward the problem of the development of novel antivirals and their delivery vehicles. In this study, we investigated the antiviral effect of the previously identified immunostimulatory 19-bp dsRNA (isRNA) with 3′-n...

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Autores principales: Goncharova, Elena P., Sen‘kova, Aleksandra V., Savin, Innokenty A., Kabilova, Tat‘yana O., Zenkova, Marina A., Vlassov, Valentin V., Chernolovskaya, Elena L.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7557936/
https://www.ncbi.nlm.nih.gov/pubmed/32937880
http://dx.doi.org/10.3390/pharmaceutics12090875
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author Goncharova, Elena P.
Sen‘kova, Aleksandra V.
Savin, Innokenty A.
Kabilova, Tat‘yana O.
Zenkova, Marina A.
Vlassov, Valentin V.
Chernolovskaya, Elena L.
author_facet Goncharova, Elena P.
Sen‘kova, Aleksandra V.
Savin, Innokenty A.
Kabilova, Tat‘yana O.
Zenkova, Marina A.
Vlassov, Valentin V.
Chernolovskaya, Elena L.
author_sort Goncharova, Elena P.
collection PubMed
description The emergence of highly pathogenic viruses and a high speed of infection spread put forward the problem of the development of novel antivirals and their delivery vehicles. In this study, we investigated the antiviral effect of the previously identified immunostimulatory 19-bp dsRNA (isRNA) with 3′-nucleotide overhangs, which stimulates interferon α synthesis when delivered using cationic liposomes consisting of 1,26-bis(cholest-5-en-3β-yloxycarbonylamino)-7,11,16,20-tetraazahexacosan tetrahydrochloride and lipid-helper dioleoylphosphatidylethanolamine and its PEGylated formulation P1500 in vitro and in vivo. In vitro data showed that isRNA/2X3-DOPE complexes protected L929 cells from encephalomyocarditis virus infection, while isRNA/P1500 complexes were not active, which correlates with their lower transfection activity in cell culture. Comparison of the interferon-inducing activity of isRNA in BALB/c, CBA and C57Bl/6 mice showed that PEGylated liposomes significantly enhance the interferon-inducing activity of isRNA in vivo. The antiviral efficacy of the isRNA in vivo was considerably affected by the delivery system. The cationic liposomes 2X3-DOPE did not enhance the antiviral properties of isRNA in vivo. Similar liposomes equipped with a PEGylated lipoconjugate provided a pronounced anti-influenza effect of the isRNA in vivo. Administration of isRNA to C57Bl/6 led to a decrease in virus titers in the lungs and a significant decrease in the severity of the infection. Administration of a similar formulation to BALB/c mice caused only a mild antiviral effect at the initial stages of the infection. The data show that isRNA in combination with the PEGylated delivery system can be considered an effective means of suppressing influenza A infection.
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spelling pubmed-75579362020-10-22 Immunostimulating RNA Delivered by P1500 PEGylated Cationic Liposomes Limits Influenza Infection in C57Bl/6 Mice Goncharova, Elena P. Sen‘kova, Aleksandra V. Savin, Innokenty A. Kabilova, Tat‘yana O. Zenkova, Marina A. Vlassov, Valentin V. Chernolovskaya, Elena L. Pharmaceutics Article The emergence of highly pathogenic viruses and a high speed of infection spread put forward the problem of the development of novel antivirals and their delivery vehicles. In this study, we investigated the antiviral effect of the previously identified immunostimulatory 19-bp dsRNA (isRNA) with 3′-nucleotide overhangs, which stimulates interferon α synthesis when delivered using cationic liposomes consisting of 1,26-bis(cholest-5-en-3β-yloxycarbonylamino)-7,11,16,20-tetraazahexacosan tetrahydrochloride and lipid-helper dioleoylphosphatidylethanolamine and its PEGylated formulation P1500 in vitro and in vivo. In vitro data showed that isRNA/2X3-DOPE complexes protected L929 cells from encephalomyocarditis virus infection, while isRNA/P1500 complexes were not active, which correlates with their lower transfection activity in cell culture. Comparison of the interferon-inducing activity of isRNA in BALB/c, CBA and C57Bl/6 mice showed that PEGylated liposomes significantly enhance the interferon-inducing activity of isRNA in vivo. The antiviral efficacy of the isRNA in vivo was considerably affected by the delivery system. The cationic liposomes 2X3-DOPE did not enhance the antiviral properties of isRNA in vivo. Similar liposomes equipped with a PEGylated lipoconjugate provided a pronounced anti-influenza effect of the isRNA in vivo. Administration of isRNA to C57Bl/6 led to a decrease in virus titers in the lungs and a significant decrease in the severity of the infection. Administration of a similar formulation to BALB/c mice caused only a mild antiviral effect at the initial stages of the infection. The data show that isRNA in combination with the PEGylated delivery system can be considered an effective means of suppressing influenza A infection. MDPI 2020-09-14 /pmc/articles/PMC7557936/ /pubmed/32937880 http://dx.doi.org/10.3390/pharmaceutics12090875 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Goncharova, Elena P.
Sen‘kova, Aleksandra V.
Savin, Innokenty A.
Kabilova, Tat‘yana O.
Zenkova, Marina A.
Vlassov, Valentin V.
Chernolovskaya, Elena L.
Immunostimulating RNA Delivered by P1500 PEGylated Cationic Liposomes Limits Influenza Infection in C57Bl/6 Mice
title Immunostimulating RNA Delivered by P1500 PEGylated Cationic Liposomes Limits Influenza Infection in C57Bl/6 Mice
title_full Immunostimulating RNA Delivered by P1500 PEGylated Cationic Liposomes Limits Influenza Infection in C57Bl/6 Mice
title_fullStr Immunostimulating RNA Delivered by P1500 PEGylated Cationic Liposomes Limits Influenza Infection in C57Bl/6 Mice
title_full_unstemmed Immunostimulating RNA Delivered by P1500 PEGylated Cationic Liposomes Limits Influenza Infection in C57Bl/6 Mice
title_short Immunostimulating RNA Delivered by P1500 PEGylated Cationic Liposomes Limits Influenza Infection in C57Bl/6 Mice
title_sort immunostimulating rna delivered by p1500 pegylated cationic liposomes limits influenza infection in c57bl/6 mice
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7557936/
https://www.ncbi.nlm.nih.gov/pubmed/32937880
http://dx.doi.org/10.3390/pharmaceutics12090875
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